This award will prepare Theoklis Zaoutis, M.D., for a career as an independent investigator in Pediatric Infectious Disease epidemiology, with a particular focus on fungal infections and the use of antimicrobial agents. He proposes a comprehensive, interdisciplinary program that will provide him with the skills, and experience necessary for independent patient-oriented research. The training component includes advanced education in clinical epidemiology and biostatistics, training in Hospital Epidemiology, and dual mentorship from an internationally recognized pharmacoepidemiologist and a renowned medical mycologist. The research component of the award will focus on candidemia and the role antibiotics may play in the development of candidemia. Infections due to Candida spp. are the most common fungal infections in hospitalized patients and the fourth most common isolate recovered in cases of nosocomial bloodstream infection in the United States. The proposal has three specific aims: Aim 1: to determine the risk factors for candidemia in children. This specific aim hypothesizes that the use of antibiotics with activity against anaerobic bacteria is associated with an increased risk of candidemia. This hypothesis will be tested using two nested case-control studies. The first study will test the hypothesis in a sample of children with cancer. The second study will test the hypothesis in a sample of children without cancer. The primary analysis will compare children with candidemia (cases) to children without candidemia (controls). Cases and controls will be matched on time at risk using incidence-density sampling. Aim 2: to develop a clinical prediction rule for candidemia in children without cancer. This specific aim will be based on the same cohort of hospitalized patients receiving antibiotics as described in SA1. Aim 3: to determine the clinical outcomes of children with candidemia. This specific aim will use a retrospective cohort design to test the hypothesis that children with candidemia caused by C. albicans have poorer clinical outcomes than children with candidemia caused by non-albicans Candida spp. The primary analysis for this aim will utilize survival analysis methods. This work may establish a rational basis for guiding antibiotic selection in high-risk children. Future studies will be planned to evaluate the effect of interventions designed to decrease the risk of developing candidemia as well as the effect of the prediction rule in selecting more effective prophylactic and preemptive therapy for children at high risk for the development of candidemia.